Overweight in Adolescence and Young Adulthood in Association With Adult Cerebrovascular Disease: The NFBC1966 Study.

BACKGROUND: Risk factors for cerebrovascular disease in adulthood are well known. However, research on individuals' risk factors throughout their life span has been limited. This prospective cohort study aims to determine the effect of body mass index (BMI) and its changes in adolescence and young adulthood on early onset cerebrovascular disease. METHODS: This study includes 10 491 people (5185 women) from the Northern Finland Birth Cohort 1966. Height, weight, and BMI were measured at ages 14 and 31 years. Sex- and age-specific BMI ranges were used to define overweight and obesity. Data on ischemic and hemorrhagic cerebrovascular diseases between ages 14 and 54 years were extracted from national hospital and death registers. Cox proportion hazard models (95% CI) were used to estimate associations between BMI or its changes and cerebrovascular disease, while adjusting for sex, smoking, educational level, BMI at the other time point, and age at menarche for women. Additionally, sex-BMI interactions were calculated. RESULTS: A total of 452 individuals (4.7%) experienced cerebrovascular disease during the follow-up. The risk of ischemic cerebrovascular disease was increased for overweight women at ages 14 years (hazard ratio [HR], 2.49 [95% CI, 1.44-4.31]) and 31 years (HR, 2.13 [95% CI, 1.14-3.97]), as well as for obese women at ages 14 years (HR, 1.87 [95% CI, 0.76-4.58) and 31 years (HR, 2.67 [95% CI, 1.26-5.65]), with normal weight as the reference. These results were independent of earlier or later BMI. Similar associations were not found among men. The risk of hemorrhagic cerebrovascular disease was increased at age 31 years both among obese women (HR, 3.49 [95% CI, 1.13-10.7) and obese men (HR, 5.75 [95% CI, 1.43-23.1). The risk of any cerebrovascular disease related to overweight at age 14 years was 2.09× higher among girls than boys (95% CI, 1.06-4.15). The risk of ischemic cerebrovascular disease related to obesity at age 31 years was 6.96× higher among women than men (95% CI, 1.36-35.7). CONCLUSIONS: Among women, being overweight in adolescence or young adulthood increases the risk of cerebrovascular disease, especially ischemic, independent of their earlier or later BMI.

Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

RISK FACTORS FOR MEDIAL AND INTIMAL INTRACRANIAL INTERNAL CAROTID ARTERY CALCIFICATION IN MEN AND WOMEN WITH CARDIOVASCULAR DISEASE. THE UCC-SMART STUDY.

INTRODUCTION: Calcifications of the intracranial internal carotid artery (iICA) can lead to an increased risk for stroke. Two types of iICA calcification are known: those affecting the tunica intima or the tunica media. In extracranial arteries, risk factors and calcification patterns are different in women and men, but little is known regarding the iICA. In this study we aimed to identify sex-specific risk profiles and medications associated to intimal and medial iICA calcification in patients with cardiovascular disease (CVD). METHODS: Participants of the UCC-SMART cohort undergoing a non-contrast head CT within six months from the study inclusion were considered (n=475). Intimal or medial iICA calcification pattern was assessed using a previously histology-validated method. Sex-stratified associations between calcification pattern and cardiovascular risk factors, laboratory parameters, and medication use were calculated using Poisson regression analysis with robust standard errors. RESULTS: 204 women and 271 men (age range 24-79 years) were included. 45.4% of men and 34.8% of women showed intimal iICA calcification, while 28.4% of men and 24.0% of women showed medial iICA calcification. Minimal or no iICA calcification was observed in 26.2% of men and in 41,2% of women (reference group). Older age was associated with both calcification patterns in women and men. In women, use of vitamin K antagonists and lipid lowering drugs were associated to medial calcification, while systolic blood pressure and glucose levels were associated to intimal calcification. In men, current smoking was associated to intimal calcification. CONCLUSIONS: Women and men with CVD show differences in risk profiles and medication use associated to intimal and medial iCA calcification.

Productivity costs of lifelong smoking-the Northern Finland Birth Cohort 1966 study.

BACKGROUND: Smoking is one of the leading causes of impaired health and mortality. Loss of paid and unpaid work and replacements due to morbidity and mortality result in productivity costs. Our aim was to investigate the productivity costs of lifelong smoking trajectories and cumulative exposure using advanced human capital method (HCM) and friction cost method (FCM). METHODS: Within the Northern Finland Birth Cohort 1966 (NFBC1966), 10 650 persons were followed from antenatal period to age 55 years. The life course of smoking behaviour was assessed with trajectory modelling and cumulative exposure with pack-years. Productivity costs were estimated with advanced HCM and FCM models by using detailed, national register-based data on care, disability, mortality, education, taxation, occupation and labour market. A two-part regression model was used to predict productivity costs associated with lifelong smoking and cumulative exposure. RESULTS: Of the six distinct smoking trajectories, lifetime smokers had the highest productivity costs followed by late starters, late adult quitters, young adult quitters and youth smokers. Never-smokers had the lowest productivity costs. The higher the number of pack-years, the higher the productivity costs. Uniform patterns were found in both men and women and when estimated with HCM and FCM. The findings were independent of other health behaviours. CONCLUSIONS: Cumulative exposure to smoking is more crucial to productivity costs than starting or ending age of smoking. This suggests that the harmful effects of smoking depend on dose and duration of smoking and are irrespective of age when smoking occurred.

Productivity costs of schizophrenia spectrum and other psychotic disorders by friction cost and human capital methods: The Northern Finland Birth Cohort 1966.

PURPOSE: Psychotic disorders are associated with substantial productivity costs; however no previous studies have compared these between schizophrenia spectrum (SSD) and other psychotic disorders (OP). The human capital method (HCM) and the friction cost method (FCM) are the two most common approaches to assess productivity costs. The HCM focuses on employees' perspectives on the costs, whereas the FCM demonstrates employers' perspectives. Studies comparing these methods when estimating the productivity costs of psychoses are lacking. METHODS: Utilizing the Northern Finland Birth Cohort 1966 with linkages to national registers, we compared the adjusted productivity costs of SSD (n = 216) and OP (n = 217). The productivity costs were estimated from ages 18 to 53 including projections to statutory retirement age using the FCM and HCM. RESULTS: When estimated via the HCM, productivity losses were higher for SSD (€193,940) than for OP (€163,080). However, when assessed using the FCM, costs were significantly lower for SSD (€2,720) than for OP (€4,430). Productivity costs varied by sex and various clinical and occupational factors. CONCLUSION: This study highlights how productivity costs vary by psychosis diagnosis. These differences should be noted when planning interventions. The low FCM estimates indicate the need of interventions before or during the early phases of psychoses. From a societal perspective, interventions are needed, particularly for those with highest HCM productivity losses, such as males with SSD. Besides psychiatric services, the roles of social services, employment agencies and occupational health care should be considered when helping individuals with psychoses to working life.

Temporal Trends and Determinants of Stroke Risk in Patients With Medically Treated Asymptomatic Carotid Stenosis.

BACKGROUND: Effectiveness of carotid procedures (surgery and stenting) in patients with asymptomatic carotid artery stenosis (ACAS) depends on the absolute risk reduction that patients might receive from these procedures. We aimed to quantify the risk of ipsilateral ischemic stroke and examined temporal trends and determinants of these risks in patients with ACAS treated conservatively. METHODS: We conducted a systematic review from inception to March 9, 2023, of peer-reviewed trials and cohort studies describing ipsilateral ischemic stroke risk in medically treated patients with ACAS of ≥50%. Risk of bias was assessed with an adapted version of the Quality in Prognosis Studies tool. We calculated the annual incidence rates of ipsilateral ischemic stroke. We explored temporal trends and associations of sex and degree of stenosis with ipsilateral ischemic stroke using Poisson metaregression analysis and incidence rate ratios, respectively. RESULTS: After screening 5915 reports, 73 studies describing ipsilateral ischemic stroke rates of 28 625 patients with midyear of recruitment ranging from 1976 to 2014 were included. The incidence of ipsilateral ischemic stroke was 0.98 (95% CI, 0.93-1.04) per 100 patient-years (median duration of follow-up, 3.3 years). The incidence decreased 24% with every 5 years more recent midyear of recruitment (rate ratio, 0.76 [95% CI, 0.73-0.78]). Incidence rates of ipsilateral ischemic stroke were lower in female patients (rate ratio, 0.74 [95% CI, 0.63-0.87]) and in patients with moderate versus severe stenosis when assessed in cohort studies, with incidence rate ratios of 0.41 ([95% CI, 0.35-0.49] cutoff, 70%) and 0.42 ([95% CI, 0.30-0.59] cutoff, 80%). CONCLUSIONS: Reported risks of ipsilateral ischemic stroke in patients with ACAS have declined 24% every 5 years from mid-1970s onward, further challenging the routine use of carotid procedures. Risks were lower in female patients and more than twice as high with severe compared with moderate ACAS. Inclusion of these findings in individualized risk assessment can help to determine the benefit of carotid procedures in selected individual patients with ACAS. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021222940.

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis.

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.

Carotid Artery Stenosis and Progression of Hemispheric Brain Atrophy: The SMART-MR Study.

INTRODUCTION: It has been hypothesized that carotid artery stenosis (CAS) may lead to greater atrophy of subserved brain regions; however, prospective studies on the impact of CAS on progression of hemispheric brain atrophy are lacking. We examined the association between CAS and progression of hemispheric brain atrophy. METHODS: We included 654 patients (57 ± 9 years) of the SMART-MR study, a prospective cohort study of patients with manifest arterial disease. Patients had baseline CAS duplex measurements and a 1.5T brain MRI at baseline and after 4 years of follow-up. Mean change in hemispheric brain volumes (% of intracranial volume [ICV]) was estimated between baseline and follow-up for left-sided and right-sided CAS across three degrees of stenosis (mild [≤29%], moderate [30-69%], and severe [≥70%]), adjusting for demographics, cerebrovascular risk factors, and brain infarcts. RESULTS: Mean decrease in left and right hemispheric brain volumes was 1.15% ICV and 0.82% ICV, respectively, over 4 years of follow-up. Severe right-sided CAS, compared to mild CAS, was associated with a greater decrease in volume of the left hemisphere (B = -0.49% ICV, 95% CI: -0.86 to -0.13) and more profoundly of the right hemisphere (B = -0.90% ICV, 95% CI: -1.27 to -0.54). This pattern was independent of cerebrovascular risk factors, brain infarcts, and white matter hyperintensities on MRI, and was also observed when accounting for the presence of severe bilateral CAS. Increasing degrees of left-sided CAS, however, was not associated with greater volume loss of the left or right hemisphere. CONCLUSIONS: Our data indicate that severe (≥70%) CAS could represent a risk factor for greater ipsilateral brain volume loss, independent of cerebrovascular risk factors, brain infarcts, or white matter hyperintensities on MRI. Further longitudinal studies in other cohorts are warranted to confirm this novel finding.

Early Childhood Growth and Risk of Adult Cerebrovascular Disease: The NFBC1966.

BACKGROUND: Low birth weight is associated with an increased risk of adulthood cerebrovascular disease (CVD). Not much is known about effects of early childhood growth. We studied whether the risk of adult CVD is associated with growth or nutritional factors during early childhood. METHODS: Within the Northern Finland Birth Cohort 1966, 11 991 persons were followed from birth to 52 years of age. CVD diagnoses were extracted from national hospital and death registers with diagnostic coding based on the World Health Organization recommendations. Cox proportional hazard models were used to estimate associations of childhood growth variables, growth trajectories (by Latent Class Growth Modeling), and nutritional factors with adult CVD, for example, ischemic and hemorrhagic strokes. The analyses were adjusted for childhood socioeconomic status and birth weight. RESULTS: A total of 453 (3.8%) CVDs were recorded during follow-up. Among females, groups with low early childhood weight and height had an increased risk for adulthood ischemic CVDs, with an adjusted hazard ratio of 1.97 (95% CI, 1.21-3.20) and 2.05 (CI, 1.11-3.81), respectively. In addition, females with body mass index over 1 SD at body mass index rebound had an increased risk for ischemic CVDs (adjusted hazard ratio, 1.90 [CI, 1.19-3.04]) compared with females with body mass index -1 to +1 SD. These associations were not found among males. CONCLUSIONS: The findings suggest that timing of weight gain during childhood is of significance for development of CVD risk among females.

Family's socioeconomic profile at birth and offspring mortality until midlife - The Northern Finland Birth Cohort 1966 study.

Family's socioeconomic profile collected prenatally is known to predict offspring mortality during early life, but it remains unclear whether it has the potential to predict offspring mortality until later life. In this study, 12,063 individuals belonging to the Northern Finland Birth Cohort 1966 were followed up from mid-pregnancy for 52 years (570,000 person years). Five distinct socioeconomic profiles were identified by latent class analysis based on mother's marital status, education, and occupation; father's occupation; number of family members; location of residence, room count, and utilities; and family's wealth. The classes were highest status families (15.4% of the population), small families (22.1%), larger families (15.4%), average wealth families (23.4%), and rural families (23.3%). Their associations to offspring mortality, via linkage to national offspring death records, were analysed by Cox regression, stratified by sex and age groups (0-19, 20-38 and 40-52 years). In total, mortality was 9.2% among male and 5.0% among female offspring. Risk for midlife mortality was higher among male offspring from larger families (hazard ratio 2.19, 95% confidence interval 1.32-3.63), average wealth families (1.66, 1.02-2.73) and rural families (1.63, 1.00-2.68), relative to offspring from highest status families. It seems that family's socioeconomic profile constructed prenatally has predictive value for midlife mortality among male offspring. Premature mortality of men and women seem to be two distinct phenomena with differing underlying factors as socioeconomic profile was not associated with mortality among female offspring.

Lost individual income due to severe health events: life-course perspective in the Northern Finland Birth Cohort 1966.

BACKGROUND: Severe health events may lead to reduced income among survivors. Importantly, individuals' risks for both severe health events and for lower income are shaped by early life course. Our aim was to consider early-life factors in determining lost individual income after stroke, heart attack and cancer between ages 18 and 50. METHODS: A population-based Northern Finland Birth Cohort 1966 (N = 12 058) was used. Early-life factors were collected since mid-pregnancy until age 16 years and used to match all persons with stroke, heart attack, or cancer (n = 995) with four controls. Registered annual individual income development 15 years before and after the event was compared between cases and propensity score matched controls using time-to-event mixed models, stratified for sex. RESULTS: Compared to controls, a new decreasing income trend emerged among women after stroke (logarithmic income per time -0.54; 95% CI -0.88 to -0.20), whereas men getting stroke showed declining earnings already by the time of the event, further declining after stroke (-1.00, -1.37 to -0.63). Getting heart attack was associated with a new declining trend both in women (-0.68; -1.28 to -0.09) and men (-0.69, -1.05 to -0.32). Income declined also among control men (-0.24, -0.34 to -0.14), who had higher income but were less educated than control women. CONCLUSIONS: Stroke and heart attack but not cancer have exogenous deleterious effects on individual economy, independently of early-life factors. The effects accelerate by time. Negative income trend in control men shows that severe health events do not explain all decrease in income.

Pregnancy Risk Factors as Predictors of Offspring Cerebrovascular Disease: The Northern Finland Birth Cohort Study 1966.

[Figure: see text].

Use of antidepressant medication and suicidal ideation-the Northern Finland Birth Cohort 1966.

OBJECTIVE: The aim was to study the association between use of antidepressant medication and suicidal ideation in different diagnostic groups in a large population-based cohort. METHODS: Information on prescribed drugs within the Northern Finland Birth Cohort 1966 was collected at the age of 31 years with postal questionnaire (N= 8218). The presence of suicidal ideation was assessed via the Hopkins Symptom Checklist-25 questionnaire. We studied associations between suicidal ideation and antidepressant medication in various diagnostic and symptom groups, and it adjusted for symptoms of depression and anxiety. RESULTS: Suicidal ideation was associated with the use of antidepressant medication in all diagnostic groups, but the association disappeared with adjustment for other symptoms of depression and anxiety. Subjects who reported insomnia and used antidepressants had suicidal ideation more commonly than did subjects who were not using antidepressants even when other symptoms were adjusted for (p = 0.02). There were no statistically significant differences between antidepressant groups or doses. CONCLUSION: In a large unselected cohort, antidepressant medication was not associated with increased suicidal ideation when other symptoms of depression and anxiety were taken into account. The assessment of insomnia might be useful for identifying individuals liable to have increased suicidal ideation while on antidepressant medication.

Sex differences in modifiable risk factors for stroke incidence and recurrence: the UCC-SMART study.

BACKGROUND AND PURPOSE: Risk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort. METHODS: Within the prospective UCC-SMART study, 13,898 patients (35% women) with atherosclerotic disease or high-risk factor profile were followed up to 23 years for stroke incidence or recurrence. Hypertension, smoking, diabetes, overweight, dyslipidemia, high alcohol use, and physical inactivity were studied as risk factors. Association between these factors and ischemic and hemorrhagic stroke incidence or recurrence was studied in women and men using Cox proportional hazard models and Poisson regression models. Women-to-men relative hazard ratios (RHR) and rate differences (RD) were estimated for each risk factor. Left-truncated age was used as timescale. RESULTS: The age-adjusted stroke incidence rate was lower in women than men (3.9 vs 4.4 per 1000 person-years), as was the age-adjusted stroke recurrence rate (10.0 vs 11.7). Hypertension and smoking were associated with stroke risk in both sexes. HDL cholesterol was associated with lower stroke incidence in women but not in men (RHR 0.49; CI 0.27-0.88; and RD 1.39; CI - 1.31 to 4.10). Overweight was associated with a lower stroke recurrence in women but not in men (RHR 0.42; CI 0.23-0.80; and RD 9.05; CI 2.78-15.32). CONCLUSIONS: In high-risk population, sex modifies the association of HDL cholesterol on stroke incidence, and the association of overweight on stroke recurrence. Our findings highlight the importance of sex-specific secondary prevention.

CLUSTERS OF PARENTAL SOCIOECONOMIC STATUS IN EARLY CHILDHOOD AND INHERITED RISK FOR CEREBROVASCULAR DISEASE UNTIL MID-LIFE - NORTHERN FINLAND BIRTH COHORT 1966.

BACKGROUND AND AIMS: The incidence of cerebrovascular disease (CVD) is rising among young adults (<55 years). The risk for CVD starts to form in early childhood and is comprised of genetic and environmental risk factors. The aim of this study is to investigate the relationship between early family socioeconomic status (SES), inherited risk, and CVD until midlife. METHODS: In the Northern Finland Birth Cohort 1966 of 12,058 children, individuals were followed from gestational period up to 54 years. We used previously published early family SES clusters, based on latent class analysis of a wide set of prenatally collected variables. We investigated inherited risk with polygenic risk score (PRS) and parental CVDs during follow-up. The associations of the five distinct clusters, inherited risk, and consequent risk for various types of CVDs until middle age were analysed with Cox regression. All analyses were conducted first in the whole sample and then stratified by sex as is recommended in cardiovascular studies. RESULTS: During the follow-up of 586,943 person-years, 512 CVDs occurred. No clear association between SES clusters and CVD were found. Higher PRS associated with any CVD (HR per 1 SD increase 1.15; 95%CI 1.02-1.31), and ischemic CVD (HR 1.21; 1.05-1.40). We found no combined associations of early family SES and inherited risk for CVD. CONCLUSIONS: Inherited risk was associated with the risk for CVD in mid-life in Finnish population. We found no clear connection with early family SES and CVD. Being born to a specific SES group did not increase the effect of inherited risk.

Imaging of intracranial arterial disease: a comparison between MRI and unenhanced CT.

Background and purpose: Arterial calcifications on unenhanced CT scans and vessel wall lesions on MRI are often used interchangeably to portray intracranial arterial disease. However, the extent of pathology depicted with each technique is unclear. We investigated the presence and distribution of these two imaging findings in patients with a history of cerebrovascular disease. Materials and methods: We analyzed CT and MRI data from 78 patients admitted for stroke or TIA at our institution. Vessel wall lesions were assessed on 7 T MRI sequences, while arterial calcifications were assessed on CT scans. The number of vessel wall lesions, severity of intracranial internal carotid artery (iICA) calcifications, and overall presence and distribution of the two imaging findings were visually assessed in the intracranial arteries. Results: At least one vessel wall lesion or arterial calcification was assessed in 69 (88%) patients. Only the iICA and vertebral arteries (VA) showed a substantial number of both calcifications and vessel wall lesions. The other vessels showed almost exclusively vessel wall lesions. The number of vessel wall lesions was associated with the severity of iICA calcification (p = 0.013). Conclusions: The number of vessel wall lesions increases with the severity of iICA calcifications. Nonetheless, the distribution of vessel wall lesions on MRI and arterial calcifications on CT shows remarkable differences. These findings support the need for a combined approach to examine intracranial arterial disease.

Ischemic stroke recurrence and mortality in different imaging phenotypes of ischemic cerebrovascular disease: The SMART-MR Study.

BACKGROUND: Diagnosis of cerebrovascular disease is based on both clinical and radiological findings, however, they do not always correlate. AIMS: To investigate ischemic stroke recurrence and mortality in patients with different imaging phenotypes of ischemic cerebrovascular disease. METHODS: Within the SMART-MR study, a prospective patient cohort with arterial disease, cerebrovascular diseases of participants at baseline were classified as no cerebrovascular disease (reference group, n = 828), symptomatic cerebrovascular disease (n = 204), covert vascular lesions (n = 156), or imaging negative ischemia (n = 90) based upon clinical and MRI findings. Ischemic strokes and deaths were collected at 6 month-intervals up to 17 years of follow-up. With Cox regression, relationships between phenotype and ischemic stroke recurrence, cardiovascular mortality, and non-vascular mortality were studied adjusted for age, sex, and cardiovascular risk factors. RESULTS: Compared to reference group risk for recurrent ischemic stroke was increased not only in the symptomatic cerebrovascular disease (HR 3.9, 95% CI 2.3-6.6), but also in the covert vascular lesion (HR 2.5, 95% CI 1.3-4.8) and the imaging negative ischemia groups (HR 2.4, 95% CI 1.1-5.5). Risk for cardiovascular mortality was increased in the symptomatic cerebrovascular disease (HR 2.2, 95% CI 1.5-3.2) and covert vascular lesions groups (HR 2.3, 95% CI 1.5-3.4), while the risk was less strong but also increased in the imaging negative ischemia group (HR 1.7, 95% CI 0.9-3.0). CONCLUSIONS: People with all imaging phenotypes of cerebrovascular disease have increased risk of recurrent ischemic stroke and mortality compared to other arterial diseases. Strict preventive measures should be performed even when imaging findings or clinical symptoms are absent. DATA ACCESS STATEMENT: For use of anonymized data, a reasonable request has to be made in writing to the UCC-SMART study group and the third party has to sign a confidentiality agreement.

Low-grade carotid artery stenosis is associated with progression of brain atrophy and cognitive decline. The SMART-MR study.

Asymptomatic low-grade carotid artery stenosis (LGCS) is a common finding in patients with manifest arterial disease, however its relationship with brain MRI changes and cognitive decline is unclear. We included 902 patients (58 ± 10 years; 81% male) enrolled in the Second Manifestations of Arterial Disease - Magnetic Resonance (SMART-MR) study without a history of cerebrovascular disease. LGCS was defined as 1-49% stenosis on baseline carotid ultrasound, whereas no LGCS (reference category) was defined as absence of carotid plaque. Brain and white matter hyperintensity (WMH) volumes and cognitive function were measured at baseline and after 4 (n = 480) and 12 years (n = 222) of follow-up. Using linear mixed-effects models, we investigated associations of LGCS with progression of brain atrophy, WMH, and cognitive decline. LGCS was associated with greater progression of global brain atrophy (estimate -0.03; 95%CI, -0.06 to -0.01; p = 0.002), and a greater decline in executive functioning (estimate -0.02; 95%CI, -0.031 to -0.01; p < 0.001) and memory (estimate -0.012; 95%CI, -0.02 to -0.001; p = 0.032), independent of demographics, cardiovascular risk factors, and incident brain infarcts on MRI. No association was observed between LGCS and progression of WMH. Our results indicate that LGCS may represent an early marker of greater future brain atrophy and cognitive decline.

Use of antipsychotic medication and suicidality--the Northern Finland Birth Cohort 1966.

In addition to psychoses, antipsychotic drugs are nowadays also prescribed for other psychiatric disturbances, such as mood disorders. We wanted to find out whether there is any association between the use of antipsychotic drugs and suicidality in cases of psychotic and non-psychotic disorders. Our sample was the population-based Northern Finland 1966 Birth Cohort. Information on the use of prescribed drugs was collected in 1997 from the nationwide medication register and with a postal questionnaire (N = 8218). The presence of suicidal ideation was assessed cross-sectionally using the Symptom Check List-25 questionnaire. We studied associations between suicidal ideation, adjusted for symptoms of depression and anxiety, and antipsychotic medication in different diagnostic groups (schizophrenia, other psychosis and no psychosis). Individuals receiving antipsychotic medication (n = 70, 0.9%) had in general more suicidal ideation regardless of diagnostic group, although the associations diminished when taking other symptoms into account. There were no statistically significant differences between those taking typical and atypical antipsychotics. In the non-psychotic group, higher antipsychotic doses were associated with more suicidal ideation even when adjusted for symptoms of depression and anxiety (p < 0.05). In the cases of schizophrenia or other forms of psychosis, no such associations were observed. Our results suggest that one should take suicidal ideation into account when prescribing antipsychotic medication, especially for off-label use.